Portable Raman Spectroscopy for the Study of Polymorphs and Monitoring Polymorphic Transitions

Importance of the topic

Polymorphism affects material properties such as stability, solubility and bioavailability in pharmaceuticals and plays a crucial role in quality control and process development.

Objectives and study overview

This work evaluates a portable Raman spectrometer for rapid identification of polymorphic forms and real-time monitoring of phase transitions. Model systems include calcium carbonate, citric acid and dextrose, with a detailed case study on the citric acid monohydrate to anhydrous transition.

Used instrumentation

• i-Raman Plus 785S portable Raman spectrometer with TE-cooled CCD detector; spectral range 65–3350 cm⁻¹
• i-Raman Prime 785S portable system with embedded tablet and STRaman technology; spectral range 150–3350 cm⁻¹
• Immersion shaft for Raman probes; 316L stainless steel body, silica window, working distance 5 mm, –55 °C to 200 °C

Methodology

Measurements used a 785 nm CleanLaze laser at 300 mW and a lab-grade Raman probe positioned 5 mm above the sample. Spectra were collected every 15–30 seconds during heating from ambient to 80 °C. Continuous data acquisition and trend analysis were performed with BWSP-21pt11 software using both single-peak monitoring and multivariate models.

Main results and discussion

Distinct spectral patterns were observed for polymorphic pairs: calcite versus aragonite, citric acid forms, and dextrose hydrates. In the citric acid experiment, the monohydrate peak at 1108 cm⁻¹ diminished while the anhydrous peak at 1146 cm⁻¹ emerged. PCA analysis of 75 spectra showed that PC1 captured 90% of variance, mirroring the single-peak trend and confirming a systematic transition across the full spectral range.

Benefits and practical applications

Portable Raman enables non-destructive, in situ polymorph screening and process analytical technology monitoring in pharmaceutical development, manufacturing and quality control due to its compact design, ease of use and high spectral specificity.

Future trends and applications

Advances may include integration with artificial intelligence for automated spectral interpretation, expanded inline and at-line monitoring in production environments, enhanced chemometric toolkits for real-time decision support and application of STRaman for non-transparent packaging analysis.

Conclusion

This study demonstrates that portable Raman spectroscopy provides a robust, sensitive and adaptable solution for polymorph identification and real-time monitoring of phase transitions, as illustrated by the citric acid monohydrate to anhydrous transformation.

References

1. E. Smith and G. Dent, Modern Raman Spectroscopy – A Practical Approach, John Wiley and Sons, Hoboken, NJ, 2005.
2. J. Huang and M. Dali, Journal of Pharmaceutical and Biomedical Analysis 86 (2013) 92–99.
3. M. Steindl et al., Chemical Engineering and Processing 44 (2005) 471–475.
4. A. Caillet, F. Puell, G. Fevotte, Chemical Engineering and Processing 47 (2008) 377–382.